Infection with GB virus C and reduced mortality among HIV-infected patients

N Engl J Med. 2001 Sep 6;345(10):715-24. doi: 10.1056/NEJMoa010398.

Abstract

Background: The flavivirus GB virus C (GBV-C, also designated hepatitis G virus) was identified in a search for hepatitis viruses, but no disease is currently known to be associated with it. We investigated the relation between coinfection with GBV-C and the long-term outcome in patients infected with the human immunodeficiency virus (HIV).

Methods: A total of 197 HIV-positive patients were followed prospectively beginning in 1993 or 1994. Of these patients, 33 (16.8 percent) tested positive for GBV-C RNA, 112 (56.9 percent) had detectable antibodies against the GBV-C envelope protein E2, and 52 (26.4 percent) had no marker of GBV-C infection and were considered unexposed. We assessed the relation between GBV-C infection and the progression of HIV disease. We also tested 169 GBV-C-positive plasma samples with a quantitative branched-chain DNA (bDNA) assay in order to investigate possible correlations between GBV-C viral load and both the CD4+ cell count and the HIV load.

Results: Among the patients who tested positive for GBV-C RNA, survival was significantly longer, and there was a slower progression to the acquired immunodeficiency syndrome (AIDS) (P<0.001 for both comparisons). Survival after the development of AIDS was also better among the GBV-C-positive patients. The association of GBV-C viremia with reduced mortality remained significant in analyses stratified according to age and CD4+ cell count. In an analysis restricted to the years after highly active antiretroviral therapy became available, the presence of GBV-C RNA remained predictive of longer survival (P=0.02). The HIV load was lower in the GBV-C-positive patients than in the GBV-C-negative patients. The GBV-C load correlated inversely with the HIV load (r=-0.33, P<0.001) but did not correlate with the CD4+ cell count.

Conclusions: Coinfection with GBV-C is associated with a reduced mortality rate in HIV-infected patients. GBV-C is not known to cause any disease, but it is possible that its presence leads to an inhibition of HIV replication. However, GBV-C infection could also be a marker for the presence of other factors that lead to a favorable HIV response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Viral / blood
  • CD4 Lymphocyte Count
  • Disease Progression
  • Female
  • Flaviviridae* / genetics
  • Flaviviridae* / immunology
  • Flaviviridae* / isolation & purification
  • HIV / isolation & purification
  • HIV Infections / complications
  • HIV Infections / mortality*
  • HIV Infections / virology
  • Hepatitis, Viral, Human / complications*
  • Hepatitis, Viral, Human / virology
  • Humans
  • Male
  • Proportional Hazards Models
  • Prospective Studies
  • RNA, Viral / analysis
  • Survival Analysis
  • Viral Load
  • Viremia

Substances

  • Antibodies, Viral
  • RNA, Viral